The home run capped off Minnesota's third straight victory.
The winning pitcher was Twins reliever Blaine Boyer (1-1). It was his first major league victory since 2010. He was the sixth Twins pitcher of the night after Mike Pelfrey started and held the Indians to one run in the first five innings.
Cleveland built the early 2-0 lead as Indians starter Corey Kluber was perfect through five innings.
The Twins finally got something going in the sixth, when Oswaldo Arcia led the inning off with a single and took second on a wild pitch. Chris Herrmann followed with a single to bring Arcia around to score. Herrmann then scored the tying run on another wild pitch.
Herrman was the only Twins player with more than one hit. He finished 2-for-4 with an RBI and a run scored.
Brandon Moss homered for Cleveland and Michael Brantley was 2-for-5.
The series will continue on Saturday when Phil Hughes (0-2) heads to the mound for Minnesota against Cleveland's Danny Salazar. First pitch is scheduled for 1:10.